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Inhibition of angiotensin II type 1 receptor partially prevents acute elevation of pulmonary arterial pressure induced by endovascular ethanol injection

Hypertension Research volume 46, pages 972–983 (2023)Cite this article

A Comment to this article was published on 03 February 2023

Abstract

This study aimed to examine whether the administration of losartan can prevent acute elevation of pulmonary arterial pressure (AEPAP) induced by endovascular ethanol injection and to assess its related mechanisms. Male swine were selected and performed with absolute ethanol endovascular injection. Saline was used as the negative control. Losartan was administered preoperatively. Pulmonary arterial pressure (PAP), femoral arterial pressure (FAP) and heart rate (HR) were monitored during operations. Venous plasma and pulmonary artery (PA) tissue were harvested for analyses. Protein level was detected by Western blotting and ELISA, whereas qRT-PCR was used in mRNA detection. H & E staining and immunohistochemistry were conducted to evaluate histopathology. Ethanol injection elevated PAP in swine. The concentration of RAS ligands was elevated in plasma (all P < 0.0001) but not in PA. The level of oxidative stress increased in both plasma and PA. MRNA level of AT1R (P < 0.01, 95% CI: 0.251–1.006), not AT2R increased in PA. Losartan failed to inhibit AEPAP after all sessions of ethanol injection, and partially reversed the ethanol-induced PA remodeling. The P38 MAPK was activated after ethanol injection and could be inhibited by losartan (P < 0.01, 95% CI: −0.391 to −0.164). Ethanol also promoted the translocation of the P40-PHOX/P47-PHOX/P67-PHOX complex and the activation of NOX, which was independent from RAS. Endovascular ethanol injection can induce AEPAP mainly by activating RAS and P38 MAPK signaling. Losartan can partially prevent AEPAP and vascular remodeling owing to the promotion of NOX activity by ethanol.

Mechanism diagram of endovascular ethanol injection-induced acute elevation of pulmonary arterial pressure (AEPAP) partially prevented by losartan. RAS: Renin–angiotensin system; AGT: angiotensinogen; Ang I: angiotensin I; ACE: angiotensin I converting enzyme; Ang II: angiotensin II. AT1R: angiotensin II type 1 receptor. NOX2: NADPH oxidase 2. PA: pulmonary artery.

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Acknowledgements

We gratefully acknowledge the generous help of Prof. Hengye Huang from School of Public Health, Shanghai Jiao Tong University School of Medicine in statistical analysis. We sincerely appreciate Prof. Wayne F. Yakes, MD, from The Yakes Vascular Malformation Center, Englewood, Colorado, the United States, for imparting the critical technology of absolute ethanol-embolization to us. We also thanked him for his pioneering and outstanding contributions to the treatment of vascular malformations.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No.81871458), the Clinical Research Program of Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (No. JYLJ202111), and the Transverse Research Project of Shanghai Ninth People’s Hospital (No. JYHX2022007).

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  1. These authors contributed equally: Yuchen Shen, Zhenfeng Wang

Authors and Affiliations

  1. Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yuchen Shen, Zhenfeng Wang, Lixin Su, Lianzhou Zheng, Yifeng Han, Xindong Fan & Deming Wang

  2. Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China

    Xiaohui Jiao

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Shen, Y., Wang, Z., Su, L. et al. Inhibition of angiotensin II type 1 receptor partially prevents acute elevation of pulmonary arterial pressure induced by endovascular ethanol injection. Hypertens Res 46, 972–983 (2023). https://doi.org/10.1038/s41440-022-01132-7

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